Janis Baird

Being big or growing fast: systematic review of size and growth in infancy and later obesity

Abstract Objectives To assess the association between infant size or growth and subsequent obesity and to determine if any association has been stable over time. Design Systematic review. Data sources Medline, Embase, bibliographies of included studies, contact with first authors of included studies and other experts. Inclusion criteria Studies that assessed the relation between infant size or growth during the first two years of life and subsequent obesity. Main outcome measure Obesity at any age after infancy. Results 24 studies met the inclusion criteria (22 cohort and two case-control studies). Of these, 18 assessed the relation between infant size and subsequent obesity, most showing that infants who were defined as “obese” or who were at the highest end of the distribution for weight or body mass index were at increased risk of obesity. Compared with non-obese infants, in those who had been obese odds ratios or relative risks for subsequent obesity ranged from 1.35 to 9.38. Ten studies assessed the relation of infant growth with subsequent obesity and most showed that infants who grew more rapidly were at increased risk of obesity. Compared with other infants, in infants with rapid growth odds ratios and relative risks of later obesity ranged from 1.17 to 5.70. Associations were consistent for obesity at different ages and for people born over a period from 1927 to 1994. Conclusions Infants who are at the highest end of the distribution for weight or body mass index or who grow rapidly during infancy are at increased risk of subsequent obesity.

Process evaluation of complex interventions: Medical Research Council guidance

Process evaluation is an essential part of designing and testing complex interventions. New MRC guidance provides a framework for conducting and reporting process evaluation studies

The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review

OBJECTIVES Patients with RA have an increased prevalence of cardiovascular disease (CVD). This is due to traditional risk factors and the effects of chronic inflammation. MTX is the first-choice DMARD in RA. We performed a systematic literature review to determine whether MTX affects the risk of CVD in patients with RA. METHODS We searched Medline, Embase, Cochrane database, database of abstracts of reviews of effects, health technology assessment and Science Citation Index from 1980 to 2008. Conference proceedings (British Society of Rheumatology, ACR and EULAR) were searched from 2005 to 2008. Papers were included if they assessed the relationship between MTX use and CVD in patients with RA. Two reviewers independently assessed each title and abstract for relevance and quality. RESULTS A total of 2420 abstracts were identified, of which 18 fulfilled the inclusion criteria. Two studies assessed the relationship between MTX use and CVD mortality, one demonstrated a significant reduction in CVD mortality and the second a trend towards reduction. Five studies considered all-cause CVD morbidity. Four demonstrated a significant reduction in CVD morbidity and the fifth a trend towards reduction. MTX use in the year prior to the development of RA decreased the risk of CVD for 3-4 years. Four studies considered myocardial infarction, one demonstrated a decreased risk and three a trend towards decreased risk with MTX use. CONCLUSION The current evidence suggests that MTX use is associated with a reduced risk of CVD events in patients with RA. This suggests that reducing the inflammation in RA using MTX not only improves disease-specific outcomes but may also reduce collateral damage such as atherosclerosis.

Vitamin D supplementation in pregnancy: a systematic review.

BACKGROUND It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. OBJECTIVES To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? METHODS We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. INCLUSION AND EXCLUSION CRITERIA SUBJECTS pregnant women or pregnant women and their offspring. EXPOSURE either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). OUTCOMES offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. RESULTS Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. LIMITATIONS Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. CONCLUSIONS The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001426. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Worked examples of alternative methods for the synthesis of qualitative and quantitative research in systematic reviews.

BackgroundThe inclusion of qualitative studies in systematic reviews poses methodological challenges. This paper presents worked examples of two methods of data synthesis (textual narrative and thematic), used in relation to one review, with the aim of enabling researchers to consider the strength of different approaches.MethodsA systematic review of lay perspectives of infant size and growth was conducted, locating 19 studies (including both qualitative and quantitative). The data extracted from these were synthesised using both a textual narrative and a thematic synthesis.ResultsThe processes of both methods are presented, showing a stepwise progression to the final synthesis. Both methods led us to similar conclusions about lay views toward infant size and growth. Differences between methods lie in the way they dealt with study quality and heterogeneity.ConclusionOn the basis of the work reported here, we consider textual narrative and thematic synthesis have strengths and weaknesses in relation to different research questions. Thematic synthesis holds most potential for hypothesis generation, but may obscure heterogeneity and quality appraisal. Textual narrative synthesis is better able to describe the scope of existing research and account for the strength of evidence, but is less good at identifying commonality.

Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review

OBJECTIVES RA is associated with early ischaemic heart disease. This appears to be driven largely by the presence of chronic inflammation. Studies suggest that treatment with disease-modifying drugs such as MTX may reduce the incidence of cardiovascular events in RA. Anti-TNF therapies significantly reduce inflammation in RA. However, the extent to which these agents also reduce cardiovascular disease (CVD) is uncertain. The purpose of this study was to explore the effect of anti-TNF agents on CVD in RA using a systematic literature review. METHODS We searched for studies of adults with RA treated with TNF antagonists where cardiovascular outcomes were recorded using MEDLINE, EMBASE, Cochrane Database, Database of Abstracts and Reviews of Effects, Health Technology Appraisal, Science Citation Index and Clinical Evidence from 1989 to 2010. Conference proceedings for the British Society of Rheumatology, ACR and EULAR between 2005 and 2009 were hand searched. Two reviewers assessed abstracts for inclusion and then quality of selected papers was assessed. RESULTS A total of 1840 abstracts were identified and 20 articles were suitable for inclusion. Information was obtained on the effect of TNF antagonists on overall CVD events, myocardial infarction, strokes and heart failure. CONCLUSION In many studies, TNF antagonists appear to reduce the likelihood of CVD in individuals with RA. Reassuringly, there does not appear to be an increased risk of cardiac failure. However, the reduction in CVD is not as consistently seen as with studies of MTX.

Testing the fetal origins hypothesis in twins: the Birmingham twin study

Aims/hypothesis. To test whether the link between birthsize and raised blood pressure or glucose tolerance is due to genetic or intrauterine factors, we studied whether differences in birthweight between pairs of monozygous and dizygous twins are associated with adult differences in blood pressure and glucose tolerance.¶Methods. A sample of 58 monozygous and 140 dizygous twins were identified from a register of births in Birmingham, United Kingdom, between 1950 and 1954. The twins had their blood pressure measured and underwent an oral glucose tolerance test.¶Results. There were no statistically significant associations between birthweight, length or ponderal index, and either blood pressure or glucose tolerance in the twins. Although there were substantial within-pair differences in birthweight between monozygous and dizygous twin pairs, these differences did not correlate with the adult outcomes. Monozygous correlations, however, for both blood pressure and glucose tolerance were statistically significantly higher than dizygous correlations and a quantitative genetic model suggested statistically significant heritability for these traits. In contrast correlations of birthsize were similar in monozygous and dizygous pairs suggesting only a small genetic component in determining fetal size.¶Conclusion/interpretation. Our results show that birthsize in twins does not predict adult blood pressure or glucose tolerance. We also suggest that shared genetic determinants for fetal growth and adult outcomes are not likely to be prevalent or powerful. [Diabetologia (2001) 44: 33–39]

Process evaluation in complex public health intervention studies: the need for guidance

Public health interventions aim to improve the health of populations or at-risk subgroups. Problems targeted by such interventions, such as diet and smoking, involve complex multifactorial aetiology. Interventions will often aim to address more than one cause simultaneously, targeting factors at multiple levels (eg, individual, interpersonal, organisational), and comprising several components which interact to affect more than one outcome.1 They will often be delivered in systems which respond in unpredictable ways to the new intervention.2 Recognition is growing that evaluations need to understand this complexity if they are to inform future intervention development, or efforts to apply the same intervention in another setting or population.1 Achieving this will require evaluators to move beyond a ‘does it work?’ focus, towards combining outcomes and process evaluation. There is no such thing as a typical process evaluation, with the term applied to studies which range from a few simple quantitative items on satisfaction, to complex mixed-method studies exploring issues such as the process of implementation, or contextual influences on implementation and outcomes. As recognised within MRC guidance for evaluating complex interventions, process evaluation may be used to ‘assess fidelity and quality of implementation , clarify causal mechanisms and identify contextual factors associated with variation in outcomes’.1 This paper briefly discusses each of these core aims for process evaluation, before describing current Medical Research Council (MRC) Population Health Sciences Research Network (PHSRN) funded work to develop guidance for process evaluations of complex public health interventions. ### Intervention implementation An important role for process evaluations is to examine the quantity and quality of what was actually implemented in practice, and why. This may inform implementation of similar interventions elsewhere, and facilitate interpretation of intervention outcomes. While notions of standardisation are central to implementation assessment, the nature of …

Dietary inequalities: what is the evidence for the effect of the neighbourhood food environment?

This review summarises the evidence for inequalities in community and consumer nutrition environments from ten previous review articles, and also assesses the evidence for the effect of the community and consumer nutrition environments on dietary intake. There is evidence for inequalities in food access in the US but trends are less apparent in other developed countries. There is a trend for greater access and availability to healthy and less healthy foods relating to better and poorer dietary outcomes respectively. Trends for price show that higher prices of healthy foods are associated with better dietary outcomes. More nuanced measures of the food environment, including multidimensional and individualised approaches, would enhance the state of the evidence and help inform future interventions.

Variations in Infant Feeding Practice Are Associated with Body Composition in Childhood: A Prospective Cohort Study

CONTEXT Most studies of infant diet and later body composition focus on milk feeding; few consider the influence of variations in the weaning diet. OBJECTIVE Our objective was to examine how variations in milk feeding and the weaning diet relate to body composition at 4 yr. STUDY POPULATION A total of 536 children participating in a prospective birth cohort study. DESIGN Diet was assessed at 6 and 12 months of age. Compliance with weaning guidance was defined by the infants score for a principal component analysis-defined dietary pattern (infant guidelines) at 12 months. Infants with high infant guidelines scores had diets characterized by high consumption of fruit, vegetables, and home-prepared foods. Body composition was assessed at 4 yr by dual x-ray absorptiometry. RESULTS Longer duration of breastfeeding was associated with lower fat mass at 4 yr [4.5 kg, 95% confidence interval (CI) of 4.3-4.7 kg, in children breastfed for 12 months or more, compared with 5.0 (95% CI 4.7-5.3) kg in children never breastfed (P = 0.002)] but was not related to body mass index. Children with high infant guidelines scores had a higher lean mass [12.6 (95% CI 12.3-12.9) kg in children in the top quarter of the distribution, compared with 12.0 (95% CI 11.7-12.4) kg in children in the bottom quarter (P = 0.001)]. These associations were independent and were little changed by adjustment for confounding factors. CONCLUSIONS These data suggest that variations in both milk feeding and in the weaning diet are linked to differences in growth and development, and they have independent influences on body composition in early childhood.